title: DNA hypermethylation of microRNA-34b/c has prognostic value for stage Ⅰ non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer-related death in the world and approximately 30-40% of patients with stage Ⅰ non-small cell lung cancer (NSCLC) die of recurrent disease. miRNA expression profiles can be diagnostic and prognostic markers of lung cancer. Recently, miR-34 family has been shown to be part of the p53 pathway which is frequently involved in lung cancer, and the expression of miR-34 has been reported to be regulated by DNA methylation. In present study, we investigated the correlation between DNA methylation status of miR-34 family and recurrence of stage Ⅰ NSCLC patients. miR-34a and miR-34b/c promoter methylation status were determined by nested methylation-specific PCR in FFPE tumor tissues from 161 patients of stage Ⅰ NSCLC. Furthermore, mature miR-34b and miR-34c expression were analyzed by qRT-PCR in the same panel tissues. Our results revealed that aberrant DNA methylation of miR-34b/c was correlated with a high probability of recurrence (p = 0.026) and associated with poor overall survival (p = 0.010) and disease-free survival (p = 0.017). No significant association was found for miR-34a methylation. Multivariate analysis showed that promoter hypermethylation of miR-34b/c was an independent prognostic factor of stage Ⅰ NSCLC. Moreover, no significant association between mature miR-34b and miR-34c expression and DNA methylation status was found. In conclusion, we have identified promoter hypermethylation of miR-34b/c as a relatively common event in NSCLC and might be a potential prognostic factor for stage Ⅰ NSCLC.
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College and Chinese Academy of Medical Sciences, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Chen
authors.forename: Yushun
authors.initials: Y
authors.lastname: Gao
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Baozhong
authors.initials: B
authors.lastname: Li
authors.forename: Fengwei
authors.initials: F
authors.lastname: Tan
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Tan
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Yuntian
authors.initials: Y
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: He
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs